This invention relates to the obtaining of the cyanogenic glycoside, the lucumin and of the related glycosides structurally similar to the first, the lucuminic acid and the lucuminamide and its hydrolytic transformations to alpha hydroxylated derivatives, the first one initially with hydroxynitrile characteristic, as the mandelonitrile, later on turning to benzaldehyde, as finally obtained; the other two related glycosides are gotten and as well transformed; the second as carboxylic acid, similar to the mandelic acid, and the third in the amide of the same last acid; both last ones hydroxylated as finally accomplished, all of the three achieved and converted primarily in an extract together of genin and sapogenins respectively that are separated by their physical properties. These are derived by chemical or enzymatic hydrolysis of the related glycosides structurally similar to the lucumin, mainly of the genus Calocarpum, Chrysophyllum and Lucuma of the family Sapotaceae, all of them with biological activities. The biological activities show up as isolated compounds or in a mixture of extractive glycosidic substances, or as hydrolytic aglycones (glycosides lacking the “sugar” moiety) extracts of the previous ones; the two groups of derived aglycones the genin and sapogenins, isolated and purified with own chemical and biological characteristics of utility in consumption products, as presented in this work and the employment forms in cosmetics and pharmaceutical dermatological compositions and as the same in substitutes uses, as exposed here in.
The sources to obtain the hydrolytic derived aglycones, last so only in chemical structure, to the glycosides, but not unavoidably in the obtaining chain, here called derived genin and sapogenins, can be several principles or tissues of the trees of the family Sapotaceae (Calocarpum sapota, C. viride, Lucuma mammosa, L. salicifolia and of some other fruit-bearing trees of the same family known as “sapotes” included Chrysophyllum), as the barks, the leaves, the flowers or the sap; but as a renewable resource it results to be the kernel tissue used in several ways, from the whole rough, crushed or milled matter; or of what is left of the kernel as solid remainder after the lipidic expression or what is left as solid residue after the lipidic extraction (for the obtaining of the oils) or for some special circumstances it is also possible to obtain the aglycones from the related glycosidic extract. These last obtaining, for their accomplishment, is possible but not in a dependent mandatory way; the only thing needed are the kernels-bearing principles, contain them as it is in a natural way, without having suffered contact with polar liquids that extract these resources; and in this way it can be proceed to the aglyconic hydrolysis, from the kernel-bearing principles; like of what is left of solid residual products of both of the lipidic expression or the extraction or of the rough kernel matter, in whole, pieces, crushed or milled.
Of the raw materials mentioned in the previous paragraph, (resources to obtain of the derived aglycones), mainly of the kernels in rough state plainly milled or crushed or cut in small pieces or those used or of some preparation of them (kernels), for the obtaining of the derived hydrolytic aglycones (originated by the glycosides structurally related to the cyanoglycoside) of the related genus.
It can also be branched of in the previous kernel-bearing aglyconic obtaining and to achieve in an isolated extract or semi-purificated state the direct substrates of the “aglyconic” hydrolysis (enzymatic hydrolysis), and obtaining the related glycosides, without trash material, and once extracted later on to continue with the related hydrolysis or it is possible to obtain the related glycosides for other uses and being employed in the manufacture of elaborated products in extract or in isolated form for topical use.
The related glycosides to the cyanoglycoside preferably are used as “enzymatic” substrates to which are practiced a hydrolysis (being able to be chemical with organic or inorganic acids), to obtain the derived hydrolytic aglycones, the genin and the sapogenins initially mentioned. More over, this form of derivation to arrive to the aglycones does not have mandatory dependence in the obtaining chain, starting from this derived related glycoside (to the cyanoglycoside) in an extract concentrate or in isolated forms.
Practically in this work, the genin and sapogenins are obtained directly from the several preparations of the kernels, previously mentioned, without stopping in the glycosides obtaining branch off; obtaining to the stage of related glycosidic extract or in an isolated form, for then to derived in the aglycones. The kernel-bearing principles for deriving to the aglycones, this with the content of related glycosides in the kernel's matter preparations, makes possible the practicing of them, the extraction of the related glycosidic and the subsequent hydrolysis and in this way to obtain the aglycones; or it is also possible straying directly in the same course of the hydrolytic transformation to the aglycones, starting from the kernel preparations; or branching of to obtain to the related glycosidic compounds or in form of an extract (to the cyanoglycoside), obtained as a whole glycosidic extract, starting from the kernel preparations and these being used in the manufacture of cosmetic and dermatological compositions. These glycosides are obtained as a related glycosidic extract to the cyanoglycoside, or these glycosides can be isolated and in this way be used in formulations; or it is also possible for later to be re-taken the obtaining of the derived hydrolytic aglycones, but instead of using some preparation of the kernels, by the use of the prepared related glycosides, practicing them the hydrolysis, in a whole glycosidic extract form, conformed by the three related glycosides; or practicing them the same hydrolysis reaction in isolated form.
The extraction techniques and the isolation procedure of the cyanogenic and related glycosides for the obtaining of the derived hydrolytic aglycones are additionally more expensive in relation to the technique that starts of the different preparations of the kernels, via the direct hydrolysis to the aglycones; by these previously mentioned treatments of these products or preparations of the kernels containing the hydrolytic substrates related glycosides, to arrive to the derived aglycone without branching off to the extraction and the isolation of the related glycosidic compounds, straying directly to the derived hydrolytic aglycones; but both coming from the same previous, prepared material resources of the kernels of the related genus, but by different ways for their obtaining.
The preference for the obtaining of the cyanogenic and related glycosides is received by the remainders of the degreased kernels; this is because its eliminated and avoided some or the entire presences of the lipids in the kernels preparation, that interfere in the more expedite purification to these related glycosides.
Also the preference for the obtaining of the derived aglycones, the extracts of genin and of sapogenins, is received by the remainders of the degreased kernels, this is the solids residual of the kernels after the lipidic expression and afterward/or by degreased solid residue of the lipidic extraction, without being restrictive the raw material that is started in this obtaining, but being of more affords because of the advantage of the preceding profit uses of the obtaining of fixed lipids that are recovered of the kernels previously.
The genin and sapogenins extracts biologically active are obtained starting from the lucumin, the cyanogenic glycoside and of the related glycosides, the lucuminic acid and the lucuminamide; “vegetables secondary metabolites” of the related genus that mainly transformed biochemically, with added enzymes of different genus (exogenous, extrageneric), adequate, appropriate and particular for the way of taking place and for their capacity to due the reactions of aglyconic hydrolytic division, processes that are achieved with the detoxificación of the lucumin (freeing from the cyanide radical), in the genin extract blended with the extract of the sapogenins that is achieved by the same and similar transformation of the other remaining related glycosides. The lucuminic acid and the lucuminamide of the “sapotes” are achieved by the previous transformation in the derived alpha hydroxylated compounds, connected to a benzylic ring (phenylic); one is gotten as a carboxylic acid, like the mandelic acid, and the other one as the amide of the derived same previous acid; as obtained in the sapogenins extract; and by another side, the obtaining of the genin derived benzaldehydic extract, as previously mentioned with similar chemical characteristic to the other two aglycones. However, both the genin and sapogenins extracts, are obtained united in a mixture of extracts, this is if having started of some preparation of the complete kernels-bearing principles, with the whole content of natural integer of cyanogenic and related glycosides.
The three aglycones mentioned above are acquired by the hydrolytic reaction of break up of the “sugar moieties” from the parent related glycosides.
The obtaining of the solid residual product of the lipidic expression here also named as “the expression crackling”, or the solid residual (remainder) product of the obtaining of the fixed total lipids; and by the other hand the obtaining of the solid (remainder) residual product of the lipidic extraction, as the same here named as “the degreased flour” or the solid residual product of the lipidic extraction, both as vegetable remainders of the “sapotes” kernels that stay as solid residual of those processes of obtaining of the lipids. This solid residual which serve as products and raw materials, respectively, for that and for this following process of this related applications, for the obtaining of the cyanogenic and related glycosides and to their derived genin and sapogenins, which are reasons of this application and of the precedent related application of patents in these processes by the same author; made up of products and raw materials that are also constituted as elaborated and initial matters respectively for this invention and the precedent.
The election technique for the obtaining of the genin and sapogenins extracts is the enzymatic hydrolysis and preferably the vegetable tissue of substrate is selected of the rough milled kernels or as a prepared of solid residuals of the presiding obtaining of the lipids, of degreasing for the obtaining of the fixed total lipids of expression and the solid residual of the lipidic extraction of these processes of the genus. Calocarpum, Chrysophyllum and Lucuma, without being restrictive for this hydrolytic obtaining the raw materials as the referred substrate of use, but being of more profitable afford in their rendition in the integral use of the kernels, as it was said previously, being able to be the same tissue of the fresh or dry rough milled kernels, or different prepared more elaborated kernels residues as those mentioned previously which are used.
The raw materials in particular of the kernels that are used mainly in the presently and precedent work are the milled kernels (seed lacking the endocarp), being able to be used rough, as such. If the product which is wanted to arrive are the derived hydrolytic aglycones it can be started of any raw material coming from the previously mentioned kernels, being able to be the rough kernels or of some preparation of the same lipid removed kernels, as the solid residuals of lipidic expression or of solid residual of lipidic extraction processes, without being practiced some extractive procedure or washes with polar solvent (as water).
As it was said previously to arrive to the derived hydrolytic aglycones it is also possible to start of the cyanogenic and related glycosidic extract, as a whole glycosides concentrate or as purified lipidic and isolated glycosides, and being able to practice the hydrolytic process afterwards. However, this last technique to arrive to these derived aglycones is relatively too expensive and without a strict dependence to be started of these glycosidic resources extracted and in a more elaborated isolated or purified form than that of the original kernels or the degreased kernel preparations. Of being required the cyanogenic and related glycosidic extract or some glycoside of these in isolated form it is the reason for which it would serve straying in the obtaining of the same ones. If its wants to arrive to the derived hydrolytic aglycone in a more economic form and in an easy and effective way, it serve for this the solids degreases residual products of the kernels (degreased by, expression or extraction), being equally feasible the isolation of the aglyconic hydrolysis products among these material resources or products obtained in the degreasing process, to the same conditions of simplicity
The hydrolytic aglyconic derives products are possible to obtain by a practice of a chemical or enzymatic hydrolysis. Preferably, the enzymatic hydrolysis is use, practiced directly to the “expression crackling” and/or “degreased flours” of the kernels.
The hydrolytic derives which are the whole extracts of genin and sapogenins of the related “sapotes” are obtained by chemical or by the other improved enzymatic hydrolysis. It is also possible to use the related glycosidic extract as raw material in the hydrolytic attainment, as later described, which is in the kernels in gross form or to use the kernels in degreased total or partially forms or it can be started with the related glycosides in isolated forms as previously mentioned.
It is also possible to use the fresh kernels or dried milled ones, without degreasing, which are alternating raw material in variants of this invention, for the obtaining of the cyanogenic and related glycosides or to derive directly in to the chemical or enzymatic hydrolysis products.
The purpose of the present invention is to put these products with the referred principles of the cyanogenic and related glycosides or of its derived hydrolytic aglycone, the genin and the sapogenins plus, the whole group of fixed lipids of Calocarpum, Chrysophyllum or Lucuma, within reach of the public in general in an ingenieriles forms by means of industrial transformations of application, which solves the technical problems in the lipidic extraction, uses that don't taken in advantage these and continue the use of the rough matters in medicinal plant and in rustic traditional other uses, for modern practice in dermatology and cosmetology, nutrition or pharmaceuticals as in other utilities like substitutes employments of the same, in a more satisfactory way and of rational use of resources not well used in coarse treatments or without being used and leaf as vegetable matter of waste.
In remote regions of the center of Mexico and more to the south, vegetable matter of Calocarpum, Chrysophyllum or Lucuma are used as medicinal remedies, cosmetics and nutritious recipes in traditional uses, it employ preparations including to the kernels. The residuals of the kernels after the “solvent extraction” of the oils (that contains the cyanogenic and related glycosides principles as in this work said) are also reported with activity against painful affections of the skin, by mean of applications like cataplasms. The bark is reported bitter, used as astringent, and that it contains the lucumin, the cyanogenic glycoside. Decoctions of the bark are taken as pectoral's aids. In Costa Rica bark and leafs tea's are administered in arteriosclerosis and hypertension. The milky sap is emetic and anti-helminthic and it has been use topically for the removal of nuisances and of fungal skin growth.
They also take decoctions of the bark of the yellow sapote as febrifuge or in eruptions of the skin. The seed is prepared as remedy for cutaneous ulcerations.
In alternating variants of the present invention, there are also found in the seeds, triterpénicos, steroidal, and cyanogenic compound like as the alpha and beta amirin, the lupeol, lanosterols or of the lucumin, free or esterified.
These plants have a great variety of nutritious and medicinal traditional uses of which the main use is the fruit pulp for their excellent flavours and in traditional recipes of high content of proteins, carbohydrates, fibres, fatty, mineral salts, vitamins; specially carotenoid compound, thiamine, riboflavin, niacin, ascorbic acid.
The vegetable matter of Calocarpum, Chrysophyllum or Lucuma are also appreciated for their high content of fixed and volatile oils present and that they also have traditional uses in the foods and in homemade remedies for the use in the skin and the hair. However all these preparations of traditional use have not been totally developed because of technical impediments concerns in the separation and isolation methods of these active principles that give these effects and taken to industrial processes and of consumption.
The volatile oils in the traditional preparations are purely with an ethereal aroma contact effect of the vegetable rough matter, that is not possible to be separate of the vegetable matter in a conventional way and also a feasible way of being transformed and separated at the present time, as in the form explained in the obtaining of the same ones in the presently work. These essential aromas (volatile oil) characteristic of the related plants that are not attractive to be obtained by the conventional techniques to achieve these insoluble aroma materials here called the genin extract (a fraction), and another gotten as soluble water fraction the sapogenins extract, that are intimately bounded to the structural matter of the plant, in particular in the inside kernel, as it turn out to be the glycosidic sapogenic (froth making) matter.
The seed is reported to be source or substitute of the perfumery fragrance “Noyeau” and of alcoholic drinks, substituting the seeds of bitter almond by peach, “peach melocoton”, apricot or “prisco, dry small peach” being the obtaining of the “sapote” kernels” in the present work different to the treatments of the previous reference.
In regions where the pulp fruit of the Calocarpum, Chrysophyllum or Lucuma is eaten copiously that is as nutritious matter thoroughly, that imperceptibly contains active ingredients for that of traditional estimates medicinal activities mentioned previously, is observed that these population conserves good conditions in their skin and the hair, attributable to the daily use or annual seasons consumption of this food. These active ingredients are also present in the rest of the plant and in the kernels, as it is said in the “popular voice”.
The fruit of Calocarpum, Chrysophyllum and Lucuma have many uses in the traditional recipes and of economic considerable rate and the non consumable parts as food have diverse uses in cosmetic, nutritious and medicinal preparations of topical, local traditional rustic use, which don't end up separating the principles and identifying the particular effects in isolated form or to separate the toxic compounds and to enable some substances of the vegetable matter. The use of the cosmetic remedies and medicinal dermatological traditional homemade use, is not possible being used in a diffused form because aesthetics reasons and of appearance that are not able to isolate the active bound matter of the vegetable matter of support of the plant (or of structure or of trash in the kernels) that intervenes in the appearance in these prepared applications of traditional use and that they limit its daily and routine use which is the most beneficial way and of more results in its appliance. The same thing happens in nutritious traditional preparation uses, starting from the kernels, which are limited because the toxic content present, which the work here presented as patent application, due resolves, returning them innocuous.
The traditional knowledge confers to the oils of the common sapote, Calocarpum sapota or to Lucuma mammosum promoter activity of the growth of the hair, however studies in the University of California in LA (Los Angeles) (1970), by means of clinical tests practiced to the oils, fail in the detection, and do not find this activity, but they confirm that the oils of Calocarpum sapota are effective to stop the fall of the hair caused by seborrheic dermatitis. We found these same activities that is attributed traditionally to the “sapotes” of promoting the growth of the hair and that badly have been attributed isolate to the fraction of oils or the phosphatidic fraction or another oily fraction of the fixed total lipids portion by its self, because a scarce or not acting independently but having it in synergy with others derived of the seed like here revealed. The present invention has found this same activity in other extracts coming from the kernels (as the same last mentioned clinical oils studies) that due present the very defined activity on the hair follicle, of increasing its growth or of increasing the transformation of hairy hair to terminal hair by the stimulation with the mentioned extracts. This extracts comes from material derived of cyanogenic and similar related glycosides or that it remains in the solid remainder after the oils or the entire of the fixed lipids or some of these oily fractions have been obtained of the vegetable matter, or as said previously, with what remains as solid residues of lipidic expression or by the degreasing with non-polar solvent (lipidic extraction) or by the obtaining of oils in rustic traditional techniques. The solid residual that is left of the vegetable matter by the lipidic expression or the solid residual that's left by the lipidic extraction, that are chemically hydrolysable or mainly enzymatically. These activities are related about derives of the cyanogenic and related glycosides. This glycosides which are structurally similar, as that extract that contains the lucumin, and of the similar glycosidic compounds, the lucuminic acid and the lucuminamide. In the present invention these active compounds are obtained and then transformed in an exogenous enzymatical hydrolyzate, giving the active aglycone extracts previously mentioned, of genin and of sapogenins with the action of stimulation of the hair follicle and of other activities like mention previously and detailed in forward pages. To this extracts of derived aglycones that we will call here the sapogenins extract for coming from a hydrolyzed glycosides which is sapogenic (or froth forming) of the family Sapotaceae (a vegetable family classification) and of the related genus of a group of fruits called “sapotes”. This extract can act in synergy with the volatile oils portion of the same plants coming from the kernels of the “sapotes” which are those who play these activities, the genin extract, a “ethereal”portion of lipids which here is also a matter of charge of claims in the present application. As the same as with the sapogenins extract or sapogenins their are also obtained in union with the genin extract that we will also indistinctly here call as genin (or the essential oil or volatile oleaginous fraction), both coming from the same cyanogenic and similar related glycosides of these present work of the “sapotes.” The genin extract is constituted as the essential oils (or to some of the essences) of the “sapotes” that together with the sapogenins extract, both properly formed as one whole extract (when it is started from the whole or total form extract of the cyanogenic and related similar glycosides, or started of some preparation of the kernels) where it is obtained as a volatile material, aromatized fraction, of insoluble and soluble matter to the water of the “sapotes” with a well defined biological activity.
Of the preliminary tests, it has been known that of the cyanogenic glycosides and related structurally similar glycosides, which are contained in the rough kernels, is of where the genin and sapogenins come from. After being practiced the expressions and/or the non polar extractions, after being recovered or left apart, the liquid lipidic portion of both processes, these glycosides remain in the solid residues; from these solids is where the extracts of the genin and the extract of the sapogenins as aglycones of these glycosidic compounds are obtained. By means of a polar extraction processes practiced to the prepared or rough kernels these glycosides are recovered; and by the cleavage hydrolysis reaction of the “sugar” moiety” of these last ones, in the extract, or in isolated form, or from the rough kernel directly and then separated is able to obtain these principles, by these work. These aglyconic hydrolytic derives, existing in the support and nutrition germinal amyloidal structure of the kernels of the “sapotes” is what is obtained of importance. It has also been possible to know that the genin constitutes an oily odoriferous aromatized principle with the characteristic aroma of the vegetable matter in an isolated intense form and that in the topical application it is mainly an rubefacients agent and selective contrairritante for some epithelia like that of the face and the hairy scalp, that alone in the applied tissue it produces irritation of hyperaemia type, heat and pruritus and is of use in cosmetology and pharmaceutical dermatological compositions and with possibility in nutritious and alternating substitute uses.
The sapogenins in combination with the genin (both ones volatiles), together with the fixed oleaginous, not volatile fraction, which in preliminary tests have demonstrated to possess synergistic activity that is about an agent with topical defoliation activity, enhanced by the other lipidic, volatile and not volatile fractions of the same “sapote” kernel, with positive effects in the renovation and stimulation of the development of the epidermis included these effects to the hair follicle; also with activity like agent of percutaneous absorption for a watery continuous phase in union to a dispersed lipidic phases or in hydrated lipidic lamellar phases or as vesicles of the liposomal type that conform them or that contain them and their feasibility to pass to deep strata of the epidermis and with the variation of furthermore different, additional bacteriostatic and fungistatic effects which are also produced by the referred extract or as purified substances.
On the whole these substances or extracts, the genin and the sapogenins or in form of isolated compounds plus with their individual activities or in synergy with a fixed lipids fraction, being able these last ones also to be of the “sapotes”, and of the cyanogenic and related structurally similar glycosides of Calocarpum, Chrysophyllum or Lucuma it is possible the industrial production of a wide range of cosmetics and of pharmaceutical products of topic use with the mentioned effects and facts with this finality, as the results of the present inventions, that are the extracts of genin and sapogenins which are also feasible being used respectively as flavouring agents and preservers against microbial growth in cosmetic and pharmaceutical compositions, in foods, like as in another alternating or substitutes uses of these extracts and derived presented here.
The objective in the matter of this invention is to make cosmetic and pharmaceutical dermatological preparations with properties of renovation of the epidermis and as promoters of the conservation of the hairy scalp and which are characterized for having substances of Calocarpum, Chrysophyllum or Lucuma, the “sapotes” as those derives of the cyanogenic and related similar glycosides, the genin and plus the sapogenins; extra by the fixed total lipids including the fixed oils, fosfolipidos (lecithins) and of non saponificable lipidic material as residuals of glycosidic triterpenic, steroidal or sterols, components of the not volatile total oleaginous fraction; and as by the same cyanogenic and related structurally similar glycosides; all with biological activity. The total fixed lipids of the “sapotes” (or the not volatile oleaginous whole fraction), with collateral or synergistic activity to the mentioned effects to the oily volatile, insoluble material; these seconds conformed by an aglycone, the genin, separated from the other derived aglycones, the sapogenins, also with volatile but soluble to the water characters respectively, that are obtained by the same and of their corresponding glycosides of where they come from and that these last ones are achieved in an extractive different processes and of their respective separations, all containing beneficial activities to minimum dose in the skin like the hydration plus the previously mentioned activities. The cyanogenic and related structurally similar glycosides of the “sapotes” appear apart from their biological activity, which are used mainly on the whole as hydrolysable substrates or in isolated or by their presence in extracts and prepared or in the treated kernels or as rough matter.